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The phosphatase PP1 sustains global transcription by promoting RNA polymerase II pause release

ABSTRACT: The phosphatase PP1 sustains global transcription by promoting RNA polymerase II pause release

PROVIDER: PRJNA1170980 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30929707_1.fastq.gz	Fastqsanger.gz
	SRR30929707_2.fastq.gz	Fastqsanger.gz
	SRR30929708_1.fastq.gz	Fastqsanger.gz
	SRR30929708_2.fastq.gz	Fastqsanger.gz
	SRR30929709_1.fastq.gz	Fastqsanger.gz

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The phosphatase PP1 sustains global transcription by promoting RNA polymerase II pause release [TT-seq]

Project description:RNA polymerase II progression from initiation to elongation is driven in part by a cascade of protein kinases acting on the core transcription machinery. Conversely, the corresponding phosphatases, notably PP2A and PP1—the most abundant serine-threonine phosphatases in cells—are thought to mainly impede polymerase progression, respectively restraining pause release at promoters and polymerase elongation at terminators. Here we reveal an unexpected role of PP1, within the PNUTS-PP1 complex, in sustaining global transcriptional activation. Acute disruption of PNUTS-PP1 leads to severe defects in the release of paused polymerase and subsequent downregulation for the majority of transcribed genes. Mechanistically, PNUTS-PP1 promotes pause release by dephosphorylating multiple substrates, including the 7SK snRNP subunit MEPCE, a known regulator of pause release. PNUTS-PP1 exhibits antagonistic functions compared to INTAC phosphatase, which generally inhibits pause release. Our research thus highlights the opposing roles of PP1 and PP2A in modulating genome-wide transcriptional pausing and gene expression.

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The phosphatase PP1 sustains global transcription by promoting RNA polymerase II pause release [RNA-seq]

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The phosphatase PP1 sustains global transcription by promoting RNA polymerase II pause release [TT-seq]

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The phosphatase PP1 sustains global transcription by promoting RNA polymerase II pause release [PRO-seq]

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The PNUTS phosphatase complex controls transcription pause release [ChIP-Seq]

Project description:Gene expression is regulated by controlling distinct steps of the transcriptional cycle, including initiation, pausing, elongation, and termination. Kinases phosphorylate RNA Polymerase II and associated factors to control transitions between these steps and act as central gene regulatory nodes. Similarly, phosphatases that dephosphorylate these components are emerging as important regulators of transcription, though their roles remain less well understood. Here we discover that the mouse PNUTS-PP1 phosphatase complex plays an essential role in controlling transcription pause release in addition to its previously described function in transcription termination. Transcription pause release by the PNUTS complex is essential for almost all RNA Pol II-dependent gene transcription, relies on its PP1 phosphatase subunit, and controls the phosphorylation of factors required for pause release and elongation. Together, these findings reveal an essential new role for a phosphatase complex in transcription pause release and shows that the PNUTS complex is essential for RNA Pol II-dependent transcription.

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The PNUTS phosphatase complex controls transcription pause release [cTT-seq]

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Project description:Gene expression is regulated by controlling distinct steps of the transcriptional cycle, including initiation, pausing, elongation, and termination. Kinases phosphorylate RNA Polymerase II and associated factors to control transitions between these steps and act as central gene regulatory nodes. Similarly, phosphatases that dephosphorylate these components are emerging as important regulators of transcription, though their roles remain less well understood. Here we discover that the PNUTS-PP1 phosphatase complex plays an essential role in controlling transcription pause release in addition to its previously described function in transcription termination. Transcription pause release by the PNUTS complex is essential for almost all RNA Pol II-dependent gene transcription, relies on its PP1 phosphatase subunit, and controls the phosphorylation of factors required for pause release and elongation. Together, this reveals an essential new role for a phosphatase complex in transcription pause release and shows that the PNUTS complex is essential for RNA Poll II-dependent transcription.

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The PNUTS phosphatase complex controls transcription pause release

Project description:The PNUTS phosphatase complex controls transcription pause release

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